Burns and trauma to the skin affect an estimated 1.25 million Americans each year. Extensive damage to the skin has serious repercussions, leading to dehydration, increased metabolic load, entry of toxic substances, immunosuppression, and wound infection. Currently, there are no full-thickness skin substitutes approved for use in treating these debilitating and life-threatening injuries. In addition to these forms of acute skin damage, chronic non-healing wounds are a significant medical problem and are expected to increase in frequency as the US population ages. The care of patients with severe skin wounds represents an enormous cost that can be reduced significantly by altering the current wound care paradigm through the cost-effective manufacture of innovative and efficacious wound care products. The proposed work will improve upon Stratatech's established production processes for StrataGraft(R) tissue, an innovative, clinically-tested skin substitute for the treatment of traumatic and chronic skin wounds. StrataGraft(R) skin tissue is produced using human dermal fibroblasts and the proprietary NIKS(R) human keratinocyte cell line, a consistent source of genetically-uniform, non-tumorigenic, pathogen-free human keratinocytes. Stratatech recently completed a Phase I/II clinical trial of StrataGraft(R) skin tissue for the temporary management of traumatic skin wounds, the results of which indicated that StrataGraft(R) tissue is well-tolerated and comparable to the standard of care for these wounds. The goal of this SBIR Phase II Competing Renewal application is to develop improved manufacturing processes for Stratatech's line of innovative, cell-based tissues. We propose to develop and optimize completely cell-derived, closed-system manufacturing conditions for production of the clinically-tested StrataGraft(R) living human skin substitute tissue. The objective of this SBIR Phase II Competing Renewal proposal represents an important step in the refinement of our manufacturing process, increasing the safety and consistency of the product, while also reducing costs and facilitating the transition to the closed and automated manufacturing systems that will be necessary to meet the growing demand for these novel wound care products. The improvements proposed in this application would be applicable to Stratatech's entire product line, including not only StrataGraft(R) tissue, but also our line of next generation, genetically-enhanced ExpressGraft" tissues, and our in vitro skin model system. PUBLIC HEALTH RELEVANCE: More than 40,000 people are hospitalized each year in the United States for burns and millions more are affected by nonhealing chronic wounds that, if left untreated, can lead to infection or even amputation. Standard treatments are unable to adequately address these problems. The goal of this SBIR Phase II Competing Renewal proposal is to develop closed-system manufacturing processes for production of Stratatech's clinically-tested StrataGraft(R) skin substitute for the treatment of acute and chronic wounds. The proposed research will refine the current manufacturing process for StrataGraft(R) skin tissue, improving product safety and consistency, reducing costs, and facilitating process scale-up. The proposed process improvements will benefit Stratatech's entire line of therapeutic products and will facilitate the commercialization of these therapies for the treatment of traumatic and chronic wounds.